Multitudinous advancements have been made to the traditional microfracture (MFx) technique, which have involved delivery of various acellular 2nd generation MFx and cellular MFx-III components to the area of cartilage defect. The relative benefits and pitfalls of these diverse modifications of MFx technique are still not widely understood. To comparatively analyze the functional, radiological, and histological outcomes, and complications of various generations of MFx available for the treatment of cartilage defects. A systematic review was performed using PubMed, EMBASE, Web of Science, Cochrane, and Scopus. Patients of any age and sex with cartilage defects undergoing any form of MFx were considered for analysis. We included only randomized controlled trials (RCTs) reporting functional, radiological, histological outcomes or complications of various generations of MFx for the management of cartilage defects. Network meta-analysis (NMA) was conducted in Stata and Cochrane's Confidence in NMA approach was utilized for appraisal of evidence. Forty-four RCTs were included in the analysis with patients of mean age of 39.40 (± 9.46) years. Upon comparing the results of the other generations with MFX-I as a constant comparator, we noted a trend towards better pain control and functional outcome (KOOS, IKDC, and Cincinnati scores) at the end of 1-, 2-, and 5-year time points with MFx-III, although the differences were not statistically significant (P > 0.05). We also noted statistically significant Magnetic resonance observation of cartilage repair tissue score in the higher generations of microfracture (weighted mean difference: 17.44, 95% confidence interval: 0.72, 34.16, P = 0.025; without significant heterogeneity) at 1 year. However, the difference was not maintained at 2 years. There was a trend towards better defect filling on MRI with the second and third generation MFx, although the difference was not statistically significant (P > 0.05). The higher generations of traditional MFx technique utilizing acellular and cellular components to augment its potential in the management of cartilage defects has shown only marginal improvement in the clinical and radiological outcomes.
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